"Emerging Drug Discovery Targets" provides a regular summary of some of the most exciting breaking information recently featured by the pharmaceutical analysts, LeadDiscovery. Information includes editorials on recently published journal articles, selected press releases and "intelligence reports". Our target audience includes business development personnel, senior management and researchers within the drug development sector as well as bioscience investors and analysts. To receive a FREE copy by email register here!

Selected press releases - January 19th-February 2nd

• Advances in novel approaches towards the treatment of cancer: Caspase inhibitors; gene therapy; monoclonal antibodies; XIAP blockade [more]

• New approaches to rheumatoid arthritis [more]

• European Regulators Grants Sildenafil Orphan Drug Designation For Pulmonary Arterial Hypertension [more]

• News listed on DailyUpdates February 3rd onwards [more]

Advances in novel approaches towards the treatment of cancer: Caspase inhibitors; gene therapy; monoclonal antibodies; XIAP blockade

Myriad Genetics' Cancer Compound MPC-6827 Causes Tumor Regression in Pancreatic Cancers: On Jan 20 Myriad Genetics announced results of preclinical testing with its new pro-apoptotic compound, MPC-6827. This novel compound was discovered through the application of a caspase-based, high throughput screening system by Maxim Pharmaceuticals, Inc. and a subsequent medicinal chemistry program. Myriad is completing the toxicology, CMC and pharmacokinetic data required for submission to the FDA to register MPC-6827 as an Investigational New Drug (IND).

Myriad tested MPC-6827 against pancreatic tumors in a xenograft mouse model and found that this candidate demonstrated a 38% inhibition of tumor growth, compared to gemcitabine (a standard first line approach to pancreatic cancer) which showed just a 17% inhibition of tumor growth. MPC-6827 also performed well in testing against other tumor types in xenograft models. In melanoma tumors, the activity of MPC-6827 was greater than that observed with paclitaxel. More significantly, MPC-6827 treated mice had twice the survival rate compared with the paclitaxel treated mice. At the conclusion of the study, 60% of the MPC-6827 treated mice had survived the cancer, versus only 30% for the paclitaxel treated group and just 10% of the controls. The improved survival with MPC-6827 treated mice versus the control animals achieved statistical significance at a value of p=0.0002. In a breast cancer xenograft model, MPC-6827 completely halted the progression of breast cancer tumors, while untreated control mice experienced a 1000% increase in tumor size.

Myriad has several anti-cancer therapeutic development programs in progress. MPC-6827 has a mechanism of action that is distinct from another advanced Myriad anti-cancer compound, MPI-176716. Both drug candidates appear effective in killing cancer cells and regressing tumors of many types, but they achieve their effect through different pathways. [more]

GenVec Presents New Data on TNFerade(TM) for Pancreatic Cancer:  On Jan 23 Nader N. Hanna, M.D. (University of Kentucky Medical Center) presented new data on GenVec's lead oncology product candidate, TNFerade(TM), at the 2004 American Society of Clinical Oncology Gastrointestinal Cancers Symposium held in San Francisco, California. TNFerade is a second generation replication-deficient adenovector, containing the human TNF-alpha gene, regulated by a radiation-inducible promoter EGR-1. TNFerade has been well tolerated in previous phase I trials.

"We are excited about the pancreatic cancer data. TNFerade continues to demonstrate a favorable safety profile and these new data from the third cohort of patients further supports a dose related improvement," commented Paul D. Kessler, M.D., GenVec's Executive Director of Clinical Research. "Upon establishing a dose, we are optimistic about moving TNFerade into a pivotal, randomized, controlled study," Dr. Kessler concluded.

Dr. Hanna's oral presentation and the poster provided data demonstrating good tolerability when administered by either endoscopic ultrasound or percutaneous injection directly to the tumor. Although the maximum tolerated dose has not yet been reached up to 67% of treated patients have shown progression-free disease after 3 months and local tumor response (greater than 25% shrinkage) has been observed in 4 of 6 treated patients [more].

Immunomedics Reports Phase II Colorectal Cancer Therapy Data at GI Cancer Symposium: On Jan 26 Immunomedics, also at the GI Cancer Symposium of the American Society of Clinical Oncology, presented data from a Phase II study involving 23 patients who had their liver metastases from colorectal cancer surgically removed. The purpose of the study was to determine the safety and efficacy of the Company's humanized monoclonal antibody against carcinoembryonic antigen (CEA), called labetuzumab, labeled with therapeutic amounts of iodine-131 (131I) and given after attempted curative surgery of liver metastases (for a full analysis of advances in the development of monoclonal antibodies click here). "These patients operated on for their liver metastases usually have a very poor outcome, with about 70% dying of their disease within five years," commented Dr. Ivan D. Horak, Executive Vice President of Research and Development, and Chief Scientific Officer, as well as a coauthor of the paper presented. With a follow-up period of over 5 years in some patients treated with labetuzumab, 11 remain alive and 3 patients have no evidence of cancer recurring." Immunomedics are now planing to seek a commercial partner for this labetuzumab while they prepare for a Phase III, multicenter trial [more]

AEG35156 Exhibits Significant Antitumor Activity Alone and In Combination with Chemotherapeutics in Preclinical Human Cancer Xenograft Models: On Jan 30 Aegera Therapeutics and Hybridon announced the presentation of preclinical data from human cancer xenograft studies using AEG35156, a proprietary XIAP antisense therapeutic being developed through a collaboration between Aegera and Hybridon. The data were presented by Dr. Jon Durkin, Aegera's Vice President of Discovery & Preclinical Development, at the American Association for Cancer Research Advances in Cancer Research Conference in Waikoloa, Hawaii, on January 29, 2004.

AEG35156 is being developed to block the cellular synthesis of XIAP, the X-linked Inhibitor of Apoptosis Protein, using Hybridon's proprietary second-generation antisense technology which is licensed to Aegera for this program. XIAP is over-expressed or dysregulated in many tumors and renders cancer cells resistant to cell death by blocking both the intrinsic and extrinsic death pathways. AEG35156 is being designed to work alone or synergistically with cytotoxic drugs to overcome this resistance of cancer cells to cell death (for a full analysis of IAP therapeutics click here). The presented studies demonstrated that AEG35156, both as a single agent and in combination with front-line chemotherapeutic agents (docetaxel, carboplatin, cisplatin), produced a dose-dependent reduction in tumor burden in preclinical models of human ovarian, prostate, and colon carcinomas. When dosed in combination with low dose docetaxel in the preclinical model, AEG35156 caused complete and persistent regression of established human prostate tumors after the course of treatment was completed. Dr. Durkin commented, "XIAP antisense has been effective in slowing or eradicating tumors in preclinical models of all human cancer types studied to date. These data provide strong support for the commencement of clinical trials of AEG35156 as a single agent, which we expect in the first quarter of 2004, and in combination with chemotherapeutic agents later this year."[more]

New approaches to rheumatoid arthritis

Rigel Pharmaceuticals selects R406 as lead drug candidate for rheumatoid arthritis: On Jan. 28 Rigel Pharmaceuticals announced the selection of R406 as its lead therapeutic compound for the treatment of rheumatoid arthritis, the chronic inflammatory disease that causes pain, swelling, loss of function in the joints and the destruction of bone and cartilage for nearly 2.1 million Americans. Rigel plans to begin human safety trials with R406 in the second half of 2004. R406 is a novel, oral syk kinase inhibitor that blocks the activation of mast cells and B cells that promote swelling and inflammatory response. Data from pre-clinical studies indicate that R406 is effective at low doses in a rodent arthritis model, and was without obvious toxicities at doses well above the effective dose.

Rheumatoid arthritis is a chronic inflammatory disease that affects multiple tissues, but typically produces its most pronounced symptoms in the joints (for a full analysis of current and emerging treatments of rheumatoid arthritis click here). It is often progressive and debilitating, preventing people from living life symptom-free. Ultimately the chronic inflammation of joints leads to the destruction of the soft tissue and erosion of the articular surfaces of the bone. The current treatment options for rheumatoid arthritis have significant potential side effects and other shortfalls, including gastrointestinal complications and kidney damage. Rheumatoid arthritis patients receive multiple drugs depending on the extent and aggressiveness of the disease. Initially, patients with a mild-to-moderate form of the disease are offered a non-steroidal anti-inflammatory (NSAID) or a Cox-2 inhibitor. These drugs address the symptoms of rheumatoid arthritis but not the underlying progressive destruction of bone and cartilage. As the disease progresses and the patient continues to deteriorate, these drugs are then layered with more potent and potentially more toxic therapies. NSAIDs are supplemented with steroids and then a DMARD such as methotrexate, an anti-cancer agent. The other major class of DMARDs is the TNF-blocking agents such as Enbrel. These drugs block only the inflammatory mediator, TNF, and are all delivered via injection. Unfortunately, the side effects (in the case of methotrexate) and delivery (in the case of the anti-TNF agents) limit their use to late in the course of the disease when the patient is in greater distress and when the disease has already caused significant bone and cartilage damage. Rigel believes that there is a significant opportunity for an oral, safe, DMARD that can be used earlier in course of the disease preventing its progression prior to major bone and cartilage destruction.

R406 is a syk kinase inhibitor that has demonstrated inhibition of mast cell and B cell activation by both IgE and IgG, thus blocking inflammatory mediators, including TNF, various interleukins, and other mediators. R406 has been shown effective in preliminary animal models of arthritis and appears to be well tolerated in preclinical studies. Rigel believes that R406 may become a first-line DMARD with greater efficacy, safety and improved delivery and patient compliance, and thus may be used early in the course of the disease before significant bone and cartilage damage occurs. [more]

European Regulators Grants Sildenafil Orphan Drug Designation For Pulmonary Arterial Hypertension

On January 28 Pfizer announced that the European Commission has granted orphan drug status to sildenafil citrate, the active ingredient in Viagra, for possible use as a treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension. PAH is a rare and potentially fatal disease. It is characterized by abnormally high blood pressures in the arteries of the lungs. Patients with PAH often become short of breath after physical exertion and the disease leads to heart failure. PAH affects two people in ten thousand but is two to three times more common in women than men and often strikes women during their child-bearing years. Left untreated, PAH will significantly reduce life expectancy. "We are pleased with the EC's decision to grant sildenafil orphan drug status," said Joseph Feczko, M.D., President Worldwide Development. "If the results of clinical trials using sildenafil to treat PAH are positive, we will move forward with the drug registration process. There is a clear need for new treatment options for patients suffering from this deadly disease." Currently, Pfizer is conducting Phase III studies using sildenafil, with results expected by mid-year. A sildenafil product for use in PAH would be marketed under a different name than Viagra [more].

Press releases featured on DailyUpdates 3rd February onwards:

Releases are added on a day by day basis - please bookmark this page and return to it at your convenience. Alternatively please register to DailyUpdates to receive daily alerts announcing new press releases and journal articles.

• Genencor to Start Phase I Study for Therapeutic Vaccine for Hepatitis B
• Bentley Pharmaceuticals Announces Results Of A Successful Phase I Study Of Intranasal Insulin In Human Volunteers
• Ecopia BioSciences Inc.'s Cancer Drug Candidate Effective Against Brain Tumour In A Preclinical Model
• Human Genome Sciences Reports Results of Phase 2 Clinical Trial of Repifermin in Patients With Cancer Therapy-Induced Mucositis
• Positive study data has been presented on Xeloda plus irinotecan for colorectal cancer
• US approves Boehringer, Pfizer smoker's lung drug
• FDA Approves Pfizer Medicine Caduet For The Treatment of Hypertension and High Cholesterol
• FDA Accepts Allos New Drug Application with Priority Review for RSR13 in Brain Metastases From Breast Cancer
• Xechem International Files For FDA Orphan Drug Status For The Treatment Of Muscular Dystrophy With MYODUR
• Abbott Laboratories Initiates Phase III Clinical Trial to Explore Use Of HUMIRA(R) (adalimumab) in Ankylosing Spondylitis
• Gilead Announces Data from Landmark Three-Year Clinical Trial of Viread; 144-Week Data Highlight Viread Efficacy, Safety and Side Effect Profile
• OvaRex Updated Phase II Trial Results to Be Presented at Plenary Session of The Society of Gynecologic Oncology
• Columbia Laboratories Reports Positive Results From Phase II Study of Lidocaine Vaginal Gel for Dysmenorrhea
• Anika knee arthritis treatment approved in U.S.
• BioCryst Receives Orphan Drug Designation for BCX-1777
• Access Pharmaceuticals, Inc. Provides an Update on Polymer Platinate AP5346
• Schering-Plough Discontinues Phase III Clinical Study Of Sarasar TM) (Lonafarnib) In Non-Small-Cell Lung Cancer
• NeoPharm Reaches Pact With FDA On Phase III "Precise" Trial
• Climara Pro(TM), Unique Therapy to Help Alleviate Menopausal Hot Flashes and Night Sweats, Now Available in Pharmacies
• Promising Results Presented for REMICADE(R) (Infliximab) in the Treatment of Psoriasis Patients With Psoriatic Arthritis
• Sinovac Biotech commences phase I clinical testing of SARS vaccine
• Aventis, Pfizer submit insulin product in Europe
• ImClone's Cancer Drug Is Back, and U.S. Approval Is Expected
• Progen Commences Third PI-88 Phase II Trial
• Sangamo BioSciences' Partner Edwards Lifesciences Files Investigational New Drug Application for Phase I/II 'AVENGE' Clinical Trial
• CAT, Genzyme announce preliminary results from trial of CAT-192 for Scleroderma
• Nabi Biopharma's Altastaph Gets FDA Orphan Drug Status
• Alteon Announces Initiation of Phase 2 Trial of ALT-711 In Endothelial Function at Johns Hopkins
• Predix Pharmaceuticals Initiates Phase I Clinical Trial Of Novel Compound Discovered In Silico
• Bristol-myers Squibb Presents Data Providing Proof-of-concept for Novel Experimental Oral Attachment Inhibitor, a Potential New Class of Antiretroviral Therapy
• TNX-355 Phase 1b Results Presented at 11th Conference on Retroviruses And Opportunistic Infections
• FDA prioritizes New Drug Application for Genasense targeting advanced melanoma
• Glaxo begins Phase 2 trial of new type of HIV drug
• Pharmasset Reports Phase 2 HIV Study Results of Reverset(TM): Once-Daily Oral Dose Reduced HIV Viral Load by 1.77 Log(10) copies/mL
• Transgene reports positive interim Phase II data from cancer vaccine programme
• Allos Begins Phase 3 Study of RSR13 in Women With Brain Metastases From Breast Cancer
• New Data Suggest Potential for Once-Daily Dosing Regimen of Kaletra(R) (Lopinavir/Ritonavir) in HIV Treatment-Naive Patients
• Tularik Begins Phase 1 Clinical Trial Of T71, A Novel Drug Candidate For The Treatment Of Obesity
• Roche Release: Landmark Study Evaluates Leading Chronic Hepatitis C Therapy In HIV Patients
• Targeted Genetics announces positive trials results of tgAAVCF for cystic fibrosis
• Altana says files for smoker's lung drug in Europe
• Germany's Merck jumps as U.S. approves Erbitux